Cytokine polymorphisms have a synergistic effect on severity of the acute sickness response to infection.
BACKGROUND
Functional polymorphisms in immune response genes are increasingly recognized as important contributors to the marked individual differences in susceptibility to and outcomes of infectious disease. The acute sickness response is a stereotypical set of illness manifestations mediated by the proinflammatory cytokines induced by many different pathogens. The genetic determinants of severity of the acute sickness response have not previously been explored.


METHODS
We examined the impact of functional polymorphisms in cytokine genes with critical roles in the early immune response (tumor necrosis factor-alpha, interleukin-6, interleukin-10, and interferon-gamma) on the severity and duration of illness following acute infection with Epstein-Barr virus, Coxiella burnetii (the causative agent of Q fever), or Ross River virus.


RESULTS
We found that the interferon-gamma +874T/A and the interleukin-10 -592C/A polymorphisms significantly affected illness severity, cytokine protein levels, and the duration of illness. These cytokine genotypes acted in synergy to potentiate their influence on disease outcomes.


CONCLUSIONS
These findings suggest that genetically determined variations in the intensity of the inflammatory response underpin the severity of the acute sickness response and predict the recovery time across varied infections.
Vollmer-Conna
Uté
U
School of Psychiatry and 2Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, Australia.
Piraino
Barbara F
BF
Cameron
Barbara
B
Davenport
Tracey
T
Hickie
Ian
I
Wakefield
Denis
D
Lloyd
Andrew R
AR
D000293:Adolescent; D000328:Adult; D000368:Aged; D018354:Alphavirus Infections / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D001483:Base Sequence; D016997:Coxiella burnetii / Q000276:immunology; D016207:Cytokines / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011778:Q Fever / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012398:Ross River virus / Q000276:immunology
D016207:Cytokines